Food And Drug Administration Action Research Articles

Dietary exposure to cadmium from six common foods in the United States.

Recently, the United States (US) Food and Drug Administration (FDA) launched a Closer to Zero Action Plan to assess the risks of and develop action levels for certain heavy metals in food including cadmium (Cd). The problem of foodborne metal contamination has taken on new urgency, thanks in part to a 2021 US Congressional Report detailing high levels of metals found in infant food. Our risk assessment aids this FDA Action Plan by estimating the American population's Cd exposures in food, by age group and consumption patterns of certain high-risk foods; and by determining circumstances in which exposures exceed tolerable daily intakes developed by policymaking groups in the US and worldwide. We found that the age groups 6-24 months and 24-60 month old are the most highly exposed to Cd in common foodstuffs. American infants and young children of these age groups who regularly consumed rice, spinach, oats, barley, potatoes, and wheat had mean Cd exposures exceeding maximum tolerable intake level was set by the Agency for Toxic Substances and Disease Registry (ATSDR). We have identified age groups at highest potential risk, and therefore of interest for developing food safety policies to improve safety of commercial food for children.

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Challenges with sex-specific subgroup analyses in oncology clinical trials for drug approvals between 2015–2020

IntroductionWomen continue to be underrepresented in oncology clinical trials, leading to poor, underpowered subgroup analyses that cannot be generalized to cancer patients in practice. In 2014, the US Food and Drug Administration (FDA) released an Action Plan, which included actions to improve the quality and reporting of demographic subgroup data. We sought to evaluate the five-year progress since the release of this report by assessing the credibility of sex-specific subgroup analyses in oncology clinical trials. MethodsWe reviewed the FDA Hematology/Oncology Approvals website for New Molecular Entities (NMEs) that were approved for adults from 2015 to 2020. Publications and their supplementary indexes were reviewed by two authors (K.J. & A.R.) against ten criteria that gauge the credibility of subgroup analyses by assessing factors related to study design, analysis, and context. One point was awarded for each criteria met, for a maximum score of 10. ResultsWe identified a total of 73 NMEs approved for cancer treatment between 2015–2020, of which 61 met our eligibility criteria. Of these, 32 studies (52 %) reported a subgroup analysis by sex and were included in our analysis. Phase 2 (41 %) and Phase 3 (53 %) studies represented most studies. No study met ≥3 credibility criteria. ConclusionOnly half the studies included in our analysis reported outcomes by sex, which suggests the activities stipulated in the 2014 US FDA Action Plan might be ineffective. This is concerning as uncredible sex-specific subgroup analyses can lead to wrongful clinical decision-making and poor patient outcomes. Policy summaryOur findings suggest sex-specific subgroup analyses in oncology are not credible and users of these data should interpret results with caution. Regulatory bodies, such as the US FDA, ought to mandate subgroup analyses by demographic groups in drug applications. Peer-reviewed journals could ensure investigators disclose study results by sex as a condition for publication.

Continual learning in medical devices: FDA's action plan and beyond

Continual learning in medical devices: FDA's action plan and beyond

Assessment of Data Sources That Support US Food and Drug Administration Medical Devices Safety Communications

Medical Device Safety Communications (MDSCs) are used by the US Food and Drug Administration (FDA) to convey important new safety information to patients and health care professionals. The sources of initial safety signals that trigger MDSCs have not been described previously. To assess the sources of initial safety signals that trigger publication of MDSCs and the potential associations among MDSC data source, type of safety issue, and subsequent FDA action. In this cross-sectional study, all MDSCs published on the FDA website between January 1, 2011, and December 31, 2019, were assessed. The MDSC characteristics, sources of initiating safety signals, regulatory approval or clearance pathways of the related medical devices, and subsequent FDA actions were collected from the FDA website. The main outcome was the distribution of sources of initial safety signals that led to publication of MDSCs. Secondary aims included exploration of potential associations among safety signal sources (direct reporting vs other), type of safety issue (death vs other), and FDA action (withdrawal vs other). A total of 93 MDSCs were evaluated. Median time from device approval to MDSC posting was 10 years (interquartile range, 6-16 years). The most common data sources that triggered MDSCs were direct reports to the FDA through the Medical Device Reporting (MDR) program (44 of 93 [47%]) followed by regulator-initiated assessments (32 [34%]). Common safety issues included patient injury (25 [27%]), potential wrong diagnoses (19 [20%]), and death (18 [19%]). Frequent FDA action after MDSC posting included recommendation for increased vigilance and caution (47 [51%]), complete device withdrawal (12 [13%]), and warnings of specific lots or clinics (12 [13%]). There was a statistically significant correlation between direct reports of adverse events to the FDA through the MDR program and risk of death as a safety issue (14 of 44 [32%] for direct reporting vs 4 of 49 [8%] for any other data sources, P = .007). In this cross-sectional study, the most common source of initial safety signals that triggered MDSCs was direct reports of real-world adverse events to the FDA through the MDR program. The delayed detection of postmarketing adverse events highlights the importance of proactive identification of emerging device-related safety issues.

The internet market for Kratom, an opioid alternative and variably legal recreational drug

BackgroundAmidst the opioid crisis, many people are turning to plant-based kratom for self-treatment of pain, opioid addiction, and for recreational use. Its legality is variable and its safety and medicinal effects are not agreed upon. It is broadly available from Internet Kratom Vendors (IKVs). MethodsAn examination of the online marketplace for kratom was conducted to provide context to the market amidst regulatory attempts by the Food and Drug Administration (FDA) and state legislatures. A complex search strategy identified 663 English-language IKVs selling kratom for home delivery. The 100 most popular were selected for in-depth content analysis. IKVs were visited once for content analysis data collection in December, 2017 and revisited in April 2018 to assess responses to FDA action. IKV website and social media profiles were coded for topics including location, payment and shipping options, age verification, health warnings and disclaimers, and grassroots advocacy regarding upcoming state/federal regulations. ResultsForty-seven percent of IKVs claimed that kratom provides pain relief, 25% claimed it provides relief from opioid withdrawal, 81% featured a disclaimer that kratom is addictive, 54% stated that kratom is not FDA approved, and 66% featured disclaimers that it was not intended for consumption. Only 5% of vendors advertised effective age verification (such as verifying age at delivery). Compliance on the vendor's part with state and local bans varied by ban location, with only 27% prohibiting sales to Rhode Island while 65% did not ship to Indiana. ConclusionsIKVs provide easy access to a wide variety of unregulated intoxicating products with poor age verification and low adherence to US state- and local-level restrictions. There is a high prevalence of vendors featuring health claims forbidden by the Food and Drug Administration. Lessons learned from regulating the Internet cigarette sales industry could be effectively applied to IKVs with future efforts.

Youth access to JUUL online: eBay sales of JUUL prior to and following FDA action

BackgroundThe novel e-cigarette product JUUL has experienced rapid market growth. The online auction site eBay has been mentioned as a source of JUUL access for youth, and the US Food...

Too Much Carrot and Not Enough Stick in New Stem Cell Oversight Trends.

Regulators are now more often distinguishing between perceived good citizens and "bad actors" in stem cell and regenerative medicine clinical research, resulting in relatively more polar, carrot-and-stick oversight approaches. Here, I discuss why there may be too much carrot and not enough stick by regulators for effective enforcement.

Can Chemical Class Approaches Replace Chemical-by-Chemical Strategies? Lessons from Recent U.S. FDA Regulatory Action on Per- And Polyfluoroalkyl Substances.

Concern about the toxicity and exposure of per- and polyfluoroalkyl substances (PFASs) is growing among scientists, regulators, and residents of contaminated communities. In 2016, the United States Food and Drug Administration (FDA) removed three food contact substances (FCSs) containing perfluorinated chemicals from the list of approved FCSs due to concerns regarding chemical safety. To investigate the significance and limitations of the FDA's regulatory action for environmental health research, advocacy, and regulation, we conducted a media analysis and qualitative interviews with a range of involved stakeholders. We find that the FDA's regulatory action represents a potential shift from chemical-by-chemical regulation toward class-based regulation, where groups of chemicals can be identified as sharing properties and risks, and are thus evaluated and regulated together. The FDA decision sets an important precedent of using a petition process to delist chemicals based on a safety standard. However, the narrow reach of this action also highlights the need for more comprehensive, precautionary chemical regulation capable of thoroughly evaluating classes of chemicals, and raises important questions about how classes of chemicals are delimited in environmental health science and regulation.

Unicorns cartoons: marketing sweet and creamy e-juice to youth

In 2009, the Food and Drug Administration (FDA) banned characterising flavours for cigarettes with the exception of menthol and tobacco.1 New regulations, released in May 2016, deemed electronic cigarettes to...

Improving the Safety and Effectiveness of Medical Device Therapy in Women.

When not enough women are included in many clinical trials, an information gap on medical device safety and effectiveness exists, which can make it difficult to detect sex-specific results. In this article we discuss potential reasons for the underrepresentation of women and the regulatory research conducted by the U.S. Food and Drug Administration (FDA) used in supporting regulatory decisions. We demonstrate that important differences in cardiovascular device performance between women and men exist. Furthermore, concrete steps are outlined on the possible ways these sex-specific results can be detected and how a recent FDA Action Plan and Guidance Document aim at encouraging female participation in clinical trials and the appropriate analysis thereof.

Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

Medical device postapproval safety monitoring: where does the United States stand?

A recent Food and Drug Administration (FDA) proposal aims to speed the evaluation process for new high-risk medical devices that are intended to address unmet medical needs,1 much like existing expedited approval processes, such as the humanitarian device exemption rule for devices intended to treat rare diseases. Such programs are strongly supported by the medical device industry and some patient advocacy groups, which have criticized the FDA for being too stringent in its evidentiary requirements for investigational devices, leading to delays in the approval of potentially helpful products.2–4 For example, in 2011, the FDA approved a transcatheter aortic valve replacement system that demonstrated significant improvements over conventional treatment options for selected patients with severe aortic stenosis.5,6 However, the United States was the 43rd country to approve the device, roughly 4 years after the European Union.7 Yet expedited approval for high-risk medical devices raises the possibility that these devices will not be as effective as predicted in their limited premarket testing or that they could cause unanticipated harms after approval.8 Of course, well-studied devices may present unexpected safety concerns years after approval,9,10 and even the most rigorous conventional premarket approval process will result in some devices later found to be unsafe or ineffective.11–13 Safety of approved medical devices and the proper scope of premarket testing remain contentious issues after recalls of several widely used devices, including popular models of implantable cardioverter defibrillator leads14,15 and metal-on-metal hip implants.16 Inherent limitations in premarket testing, along with the prospect of lowered evidentiary standards for expedited device reviews, place greater pressures on postapproval monitoring of devices to follow clinical performance and to identify emerging public health problems. Medical device manufacturers routinely perform this sort of vigilance, …

Teen tobacco use: research and regulatory gaps.

Teen tobacco use: research and regulatory gaps.

U.S. Food and Drug Administration inspections of clinical investigators: overview of results from 1977 to 2009.

The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research is responsible for evaluating drug safety and efficacy, including oversight of clinical trials and principal investigators. The FDA Clinical Investigator Inspection List (CIIL) contains online, detailed, relevant information of all FDA inspections. We reviewed FDA inspections of clinical investigators to ascertain their outcome and included all inspections on the list (July 1977 through December 31, 2009; n = 9,481 inspections). Eighty-eight percent of inspections were "data audit" (primary purpose = verification of data), and the rest (12%) were "for cause." The number of inspections each year significantly increased over time (P < 0.0001) and averaged 350 per year in the past decade. No deficiencies were found in only 11.2% of all "data audit" and 5% of all "for cause" inspections. Only 31% of inspections resulted in "no action indicated." About two thirds of inspections resulted in some finding, requiring either voluntary investigator action (61.3% of inspections) or official FDA action (3.9%). The most frequently cited deficiencies were failure to follow investigational plan (34%), inadequate informed consent form (28%), and inadequate/inaccurate records (27%). In conclusion, over the past decade, the FDA has performed approximately 350 inspections per year, with the number increasing over time. The vast majority of FDA inspections yield deficiency findings and, as a result, only about one third of inspections have an outcome of "no action indicated."

The FDA and prescription pancreatic enzyme product cost.

The FDA and prescription pancreatic enzyme product cost.

Public opinion about FDA regulation of menthol and nicotine

ObjectiveRegulations that reduce nicotine and eliminate menthol in cigarettes have been proposed to the US Food and Drug Administration (FDA) as product alterations that could reduce smoking prevalence in the...

Reflections on the US FDA's Warning on Direct-to-Consumer Genetic Testing.

In November 2013, the US Food and Drug Administration (FDA) sent a warning letter to 23andMe, Inc. and ordered the company to discontinue marketing of the 23andMe Personal Genome Service (PGS) until it receives FDA marketing authorization for the device. The FDA considers the PGS as an unclassified medical device, which requires premarket approval or de novo classification. Opponents of the FDA's action expressed their concerns, saying that the FDA is overcautious and paternalistic, which violates consumers' rights and might stifle the consumer genomics field itself, and insisted that the agency should not restrict direct-to-consumer (DTC) genomic testing without empirical evidence of harm. Proponents support the agency's action as protection of consumers from potentially invalid and almost useless information. This action was also significant, since it reflected the FDA's attitude towards medical application of next-generation sequencing techniques. In this review, we followed up on the FDA-23andMe incident and evaluated the problems and prospects for DTC genetic testing.

An evaluation of lead concentrations in imported hot sauces

In the last decade, the U.S. Food and Drug Administration (FDA) has issued several warnings and recalls for food products that exceed FDA standards for lead. Products containing chili peppers and salt were often suspected as sources of lead contamination, and included items such as candy that are routinely investigated. However, products such as hot sauces that contain similar ingredients have not been the focus of evaluations. This study quantified lead concentrations in imported hot sauces, evaluated product compliance to existing United States standards, and calculated potential dietary lead exposure for children using the Integrated Exposure Uptake Biokinetic Model. Finally, recommendations for reducing the risk of lead exposure from hot sauces are provided. Twenty-five (25) bottles of imported hot sauces manufactured in Mexico and South America were purchased in Clark County, Nevada. All hot sauces were analyzed for lead concentrations, pH, and leaded packaging. Hot sauces were analyzed by inductively coupled plasma mass spectrometry and packaging was analyzed using x-ray fluorescence technology. Four brands of hot sauces (16%) exceeded 0.1 ppm lead, the current FDA action level for lead in candy. Hot sauces with lead concentrations >0.1 ppm lead contained salt and were manufactured in Mexico. Subsequent analysis of additional lots of hot sauces exceeding 0.1 ppm lead revealed inconsistent lead concentrations between and within manufacturer lots. The lead concentrations of the plastic hot sauce lids ranged from below the limit of detection to 2,028 ppm lead. There was no association between lead concentrations in hot sauces and pepper type. These results indicate the need for more rigorous screening protocols for products imported from Mexico, the establishment of an applicable standard for hot sauce, and resources to allow for the enforcement of existing food safety policies. The data reported herein represent the first known investigation of lead concentrations in hot sauces.

Prevention of Fatal Opioid Overdose

Prevention of Fatal Opioid Overdose